Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Keywords
siRNA, PNH
Brief summary
The first-in-human Phase 1/Phase 2a study described herein will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-038 in both healthy participants (HP) and in patients with paroxysmal nocturnal hemoglobinuria (PNH).
Detailed description
The clinical study described in this protocol is a Phase 1/Phase 2a study evaluating safety, tolerability, PK, and PD of ADX-038. The study consists of 2 parts: 1. Phase 1 - Randomized, double-blind, placebo-controlled, parallel group, single ascending dose (SAD) in HP with up to 5 dose cohorts. 2. Phase 2a - Open label, single-arm (ADX-038), 2 dose study in participants with paroxysmal nocturnal hemoglobinuria (PNH) and residual anemia on a standard-of-care (SOC) anti-C5 regimen of ravulizumab or eculizumab.
Interventions
DRUGADX-038
siRNA duplex oligonucleotide
DRUGPlacebo
Saline
Sponsors
ADARx Pharmaceuticals, Inc.
ADARx Australia Pty Ltd
Novotech (Australia) Pty Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Masking is only applicable to Phase 1 in HP. Phase 2a is open label and there is no masking.
Intervention model description
Model Description
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Phase 1 Key Inclusion Criteria * 18 to 55 years of age * Participants who are healthy as determined by medical evaluation * History of recent meningococcal, pneumococcal and Haemophilus influenzae type B vaccinations or willing to be vaccinated * Screening tests negative for illicit drug, nicotine, and alcohol use Phase 1 Key
Exclusion criteria
* History of any significant medical conditions, except for completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia without evidence of recurrence within the prior 3 months * Any viral, bacterial, parasitic, or fungal infection within the prior 30 days * Frequent respiratory, nasopharyngeal or ear infections (more than 5 infections per year) * History of environmental exposure or sick contact that increase the risk of meningococcal, pneumococcal and/or Haemophilus influenza type B infections * Complement deficiency or immunodeficiency syndrome * Major surgery or significant traumatic injury within the prior 3 months * History of anaphylaxis or hypersensitivity reactions * History of penicillin allergy * History of splenectomy * History of alcohol abuse or illicit drug use * Donated plasma within the prior 7 days * Donated blood or loss more than 400 milliliters of blood (excluding blood volume drawn at screening) within the prior 90 days * Screening estimated creatinine clearance of less than 60 milliliters per minute * Screening hematology, serum chemistry, or coagulation parameters that are outside the normal range * Screening vital signs that are abnormal per protocol specification * Screening electrocardiogram findings that are clinically significant * Pregnant or lactating females * Use of prescription (except for contraceptives and study-related prophylactic antibiotics) or over-the counter medications (except for paracetamol or ibuprofen) or vitamins/supplements within the prior 7 days * Use of medications that may reduce the effectiveness of hormonal contraceptives within the prior 28 days * Use of an investigational therapeutics within the prior 30 days or within the expected washout (at least 5 half-lives) * Unwilling or unable to adhere to study-related prophylactic antibiotics requirements Phase 2a Key Inclusion Criteria * at least 18 years of age * Diagnosis of paroxysmal nocturnal hemoglobinuria based on documented clone size * Hemoglobin concentration of less than 12 gram per deciliter * History of recent meningococcal, pneumococcal and Haemophilus influenzae type b vaccinations or willing to be vaccinated * On a stable anti-C5 regimen for greater than or equal to 12 weeks prior to Day 1 Phase 2a Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety in Healthy Volunteers | 365 days | To evaluate the safety and tolerability of ADX-038 in HVs by incidence, relationship, and severity of adverse events and serious adverse events |
| Safety in Paroxysmal Nocturnal Hemoglobinuria Participants | 365 days | Evaluate the safety and tolerability of ADX-038 by incidence, relationship, and treatment-emergent adverse events and serious adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics in Healthy Participants | 8 days | To characterize the Pharmacokinetics of ADX-038 in HPs by measuring the Maximum observed plasma concentration (Cmax) |
| Pharmacodynamics in Healthy Participants | 365 days | Change from base in plasma concentrations over time in Complement factor B (CFB) protein via assay measurement |
| Pharmacodynamics in Paraxysmal Nocturnal Hemoglobinuria | 365 days | Evaluate the changes in hemoglobin concentrations |
Countries
Australia, United Kingdom
Contacts
CONTACTStephanie Leyva
Outcome results
None listed